OBJECTIVES: This application proposes to study the effects of prenatal exposure to the tricyclic antidepressant doxepin HCl, on the subsequent development of normal function of the catecholamine, neuroendocrine and cardiovascular systems in the laboratory rat. Our proposed methods incorporate both the measured levels of doxepin achieved in the fetus in response to maternal doxepin treatment and a subsequent analysis of possible impairment of several physiologic processes. In one set of experiments, doxepin HCl (or saline control) would be administered to female rats during the first, second or final week of or throughout pregnancy and levels of doxepin and a major metabolite, desmethyldoxepin, would be determined in the fetuses. In another set of experiments, doxepin exposed and control pups would be allowed to mature. In those animals, tests would be performed to determine the state of function of the neuroendocrine, cardiovascular and central nervous catecholaminergic systems. This experimental design would allow the determination of: (1) distribution of doxepin to the fetus and the fetal tissue levels achieved following maternal administration of the drug, (2) the relationship between concentration of doxepin in fetal tissue and possible subsequent impairment of physiologic function, (3) a differentiation of the time of fetal exposure (early, middle or late) and possible subsequent impairment of physiologic functions, and (4) whether the placental barrier acts as a one or two way membrane with regards to doxepin distribution; (i.e., accumulation).